Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 13896 | 41911;41912;41913 | chr2:178635638;178635637;178635636 | chr2:179500365;179500364;179500363 |
| N2AB | 12255 | 36988;36989;36990 | chr2:178635638;178635637;178635636 | chr2:179500365;179500364;179500363 |
| N2A | 11328 | 34207;34208;34209 | chr2:178635638;178635637;178635636 | chr2:179500365;179500364;179500363 |
| N2B | 4831 | 14716;14717;14718 | chr2:178635638;178635637;178635636 | chr2:179500365;179500364;179500363 |
| Novex-1 | 4956 | 15091;15092;15093 | chr2:178635638;178635637;178635636 | chr2:179500365;179500364;179500363 |
| Novex-2 | 5023 | 15292;15293;15294 | chr2:178635638;178635637;178635636 | chr2:179500365;179500364;179500363 |
| Novex-3 | None | None | chr2:None | chr2:None |
Information
Reported SAVs
| SNV | RS | DUET |
PolyPhen-2 |
Condel |
Rhapsody |
REVEL |
MVP |
Source |
MAF |
Disease |
Zygosity |
Site annotation |
mCSM PPI |
Predicted PPI site |
Comments |
AFR |
AMR |
AMS |
ASJ |
EAS |
EUR |
FIN |
MDE |
NFE |
SAS |
OTH |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/N | rs371312327  |
-1.438 | 0.013 | N | 0.527 | 0.084 | None | gnomAD-2.1.1 | 4.49E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 1.01E-05 | 0 |
| D/V | None | None | None | N | 0.454 | 0.104 | 0.207176502487 | gnomAD-4.0.0 | 1.63394E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.93112E-06 | 0 | 0 |
Saturation Mutagenesis
SAV |
AlphaMissense (IC) |
AlphaMissense Class (IC) |
AlphaMissense (N2AB) |
AlphaMissense Class (N2AB) |
mCSM |
mCSM class |
PolyPhen-2 |
PolyPhen-2 Class |
Rhapsody |
Rhapsody Class |
Condel |
Condel Score |
Site annotation |
mCSM PPI |
Predicted PPI site |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/A | 0.1982 | likely_benign | 0.2632 | benign | -0.482 | Destabilizing | 0.006 | N | 0.499 | neutral | N | 0.439832885 | None | None | N |
| D/C | 0.6102 | likely_pathogenic | 0.7513 | pathogenic | -0.42 | Destabilizing | 0.492 | N | 0.665 | prob.neutral | None | None | None | None | N |
| D/E | 0.183 | likely_benign | 0.2349 | benign | -0.812 | Destabilizing | None | N | 0.192 | neutral | N | 0.390403486 | None | None | N |
| D/F | 0.4869 | ambiguous | 0.599 | pathogenic | -0.19 | Destabilizing | 0.112 | N | 0.679 | prob.neutral | None | None | None | None | N |
| D/G | 0.3446 | ambiguous | 0.4888 | ambiguous | -0.836 | Destabilizing | 0.026 | N | 0.565 | neutral | N | 0.443583505 | None | None | N |
| D/H | 0.1833 | likely_benign | 0.2782 | benign | -0.759 | Destabilizing | None | N | 0.306 | neutral | N | 0.443583505 | None | None | N |
| D/I | 0.205 | likely_benign | 0.2398 | benign | 0.454 | Stabilizing | 0.006 | N | 0.663 | prob.neutral | None | None | None | None | N |
| D/K | 0.4376 | ambiguous | 0.5887 | pathogenic | -1.047 | Destabilizing | 0.018 | N | 0.564 | neutral | None | None | None | None | N |
| D/L | 0.3417 | ambiguous | 0.4308 | ambiguous | 0.454 | Stabilizing | 0.018 | N | 0.563 | neutral | None | None | None | None | N |
| D/M | 0.5225 | ambiguous | 0.61 | pathogenic | 0.887 | Stabilizing | 0.112 | N | 0.647 | neutral | None | None | None | None | N |
| D/N | 0.0934 | likely_benign | 0.1215 | benign | -1.241 | Destabilizing | 0.013 | N | 0.527 | neutral | N | 0.441955121 | None | None | N |
| D/P | 0.911 | likely_pathogenic | 0.9539 | pathogenic | 0.167 | Stabilizing | 0.204 | N | 0.629 | neutral | None | None | None | None | N |
| D/Q | 0.311 | likely_benign | 0.429 | ambiguous | -1.054 | Destabilizing | 0.001 | N | 0.293 | neutral | None | None | None | None | N |
| D/R | 0.4412 | ambiguous | 0.5982 | pathogenic | -0.902 | Destabilizing | 0.035 | N | 0.625 | neutral | None | None | None | None | N |
| D/S | 0.1343 | likely_benign | 0.1816 | benign | -1.531 | Destabilizing | 0.035 | N | 0.484 | neutral | None | None | None | None | N |
| D/T | 0.2078 | likely_benign | 0.2592 | benign | -1.259 | Destabilizing | 0.018 | N | 0.597 | neutral | None | None | None | None | N |
| D/V | 0.131 | likely_benign | 0.153 | benign | 0.167 | Stabilizing | None | N | 0.454 | neutral | N | 0.447020548 | None | None | N |
| D/W | 0.8759 | likely_pathogenic | 0.9192 | pathogenic | -0.177 | Destabilizing | 0.747 | D | 0.684 | prob.delet. | None | None | None | None | N |
| D/Y | 0.1941 | likely_benign | 0.2611 | benign | -0.059 | Destabilizing | 0.046 | N | 0.685 | prob.delet. | N | 0.443583505 | None | None | N |
Titin has multiple isoforms, the longest being the theoretical IC (inferred complete) isoform which contains all 363 in-frame titin exons. Here all isoform positions have been mapped onto the IC sequence, with an exception being the C-terminal of the much shorter novex-3 isoform. This contains the out of frame exon 48 which cannot be mapped to the other isoforms.